Although alcohol is known to affect the excitability of the nervous system, the mechanisms involved in those actions are poorly understood. This project studied the cellular and molecular mechanisms regulating nerve cell excitability and the effects of ethanol on those mechanisms. The membrane ion channels that are involved in the intrinsic regulation of neuronal excitability were investigated using the whole-cell patch-clamp technique. In neurons that exhibit burst-firing behavior, generation of an action potential elicited a large depolarizing afterpotential that triggered the firing of a burst of action potentials. Voltage-clamp analysis revealed that the depolarizing afterpotential was generated by a large transient (T-type) calcium current. The burst-firing behavior developed postnatally, in contrast to the long-lasting (L-type) calcium current which did not change significantly in amplitude during development. To identify the types of isolated neurons that exhibit various patterns of firing behavior, the fluorescent dyes fast blue and fluorogold were injected in the distribution field of various types of axons and time allowed for retrograde transport. The dyes were retained after isolation of the neuronal soma, permitting identification of various neuronal types. The regulation of excitability was studied by culturing adult mammalian sensory neurons in a medium free of serum and added growth-factors. Under these conditions, the neurons retained electrical excitability and voltage-activated sodium current was tetrodotoxin (TTX)-sensitive in all neurons tested. By contrast, freshly isolated neurons and neurons cultured in the presence of nerve growth factor (NGF) exhibited TTX-resistant sodium currents in some neurons and TTX-sensitive sodium currents in others. The results suggest that NGF may regulate the expression of TTX-resistant sodium channels. Ethanol was tested on several voltage-activated ion channels and found to have little or no effect in concentrations less than 100 mM.